This application regards funding of an exploratory international collaboration to study the genetic and neurobiological underpinnings of alcohol-seeking behavior. The collaborating sites are the Indiana University Alcohol Research Center (IARC) in Indianapolis, USA, and the Addiction Research Foundation (ARF) in Toronto, Canada. Both have established alcohol researchers who will bring unique resources and expertise to this collaborative effort. The unique resource ARF brings to the project are the selectively-bred alcohol- preferring HARF and nonpreferring IARF rat lines that are being developed, based on the limited-access drinking paradigm to mimic binge drinking. The unique resource IARC brings to the project are the high alcohol-preferring HAD and low alcohol-preferring LAD rat lines, selected on the basis of 24 h. free-choice (continuous access) consumption of 10% ethanol. Importantly, both pairs of selected lines originate from the same heterogeneous stock N/Nih rat. The collaboration, therefore, represents an unprecedented opportunity to compare and contrast the behavioral and neurobiological traits that are associated with the two differently selected drinking phenotypes, as a way of uncovering potentially common mechanisms. To initiate the collaboration, we will address the important question of alcohol- nicotine interaction and bring to the collaboration the laboratory resources and expertise of William Corrigall, a pioneer in studying nicotine self-administration by the laboratory animal. We propose studies to examine if line differences exist in: l) the acute effects of nicotine and ethanol on spontaneous locomotor activity and body temperature; 2) development of sensitization to the effects of nicotine and ethanol on locomotor activity following repeated nicotine or ethanol administration; 3) the effects of acute and chronic nicotine pretreatment on alcohol consumption; and 4) the rate of acquisition and extent of IV nicotine self-administration.